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Showing H2AC4 — HIST1H2AB is a alias.

H2AC4

Histone H2A type 1-B/E · UniProt P04908

Length
130 aa
Mass
14.1 kDa
Annotated
2026-06-10
37 papers in source corpus 1 papers cited in narrative 1 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

H2AC4 (HIST1H2AB), a histone H2A family member, has been characterized in the available corpus primarily through its role in lung adenocarcinoma, where its knockdown inhibits proliferation, promotes apoptosis, and delays xenograft tumor growth (PMID:36511295). Gene expression profiling links H2AC4 to regulation of the interferon signaling pathway and downstream genes including HMGB1, FOXM1, F2RL1, and SLC4A7 (PMID:36511295). Beyond this oncogenic association, no detailed molecular mechanism for the canonical H2AC4 protein has been established in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2023 Medium

    Whether H2AC4 contributes functionally to cancer was unknown; loss-of-function established it as a pro-proliferative, anti-apoptotic factor in lung adenocarcinoma and tied it to interferon-pathway gene regulation.

    Evidence shRNA knockdown with colony formation and Annexin V apoptosis assays in A549 and H1299 cells, xenograft mouse model, and gene expression array with RT-qPCR/western validation

    PMID:36511295

    Open questions at the time
    • No direct biochemical mechanism linking the histone to interferon-pathway or HMGB1/FOXM1/F2RL1/SLC4A7 regulation
    • Single lab, no reconstitution or rescue of the knockdown phenotype
    • No structural or chromatin-level characterization of the canonical protein

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular function of H2AC4 as a nucleosomal histone and the mechanism by which its levels influence the interferon signaling axis remain uncharacterized.
  • No direct evidence that H2AC4 incorporation into chromatin drives the observed transcriptional changes
  • No interaction partners or post-translational modifications defined in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 HIST1H2AB (H2AC4) knockdown inhibited proliferation and promoted apoptosis of lung adenocarcinoma cells (A549 and H1299) in vitro and delayed tumor growth in xenograft models. Gene expression array analysis suggested that HIST1H2AB regulates the interferon signaling pathway and genes including HMGB1, FOXM1, F2RL1, and SLC4A7 in lung adenocarcinoma. shRNA-mediated knockdown, colony formation assay, Annexin V apoptosis assay, xenograft mouse model, human gene expression array, RT-qPCR, western blotting The journal of gene medicine Medium 36511295

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. The Journal of biological chemistry 307 15073169
2021 Dynamic transcriptomic m5 C and its regulatory role in RNA processing. Wiley interdisciplinary reviews. RNA 244 33438329
2005 Phosphorylation of histone H2AX at M phase in human cells without DNA damage response. Biochemical and biophysical research communications 125 16153602
2006 Therapeutic targets and potential of the novel brain- permeable multifunctional iron chelator-monoamine oxidase inhibitor drug, M-30, for the treatment of Alzheimer's disease. Journal of neurochemistry 117 17144902
2007 Neurorescue activity, APP regulation and amyloid-beta peptide reduction by novel multi-functional brain permeable iron- chelating- antioxidants, M-30 and green tea polyphenol, EGCG. Current Alzheimer research 87 17908043
1999 A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division. Proceedings of the National Academy of Sciences of the United States of America 84 10077596
2006 Benzyl isothiocyanate-induced DNA damage causes G2/M cell cycle arrest and apoptosis in human pancreatic cancer cells. The Journal of nutrition 72 17056792
2024 RNA m5C oxidation by TET2 regulates chromatin state and leukaemogenesis. Nature 64 39358506
2015 Comparative transcriptome profiling of Pyropia yezoensis (Ueda) M.S. Hwang & H.G. Choi in response to temperature stresses. BMC genomics 47 26081586
2016 Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle arrest and apoptosis in human papillary thyroid carcinoma BCPAP cells. Food & function 46 26442630
2013 4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway. The Journal of biological chemistry 45 23733185
2015 Chromatin remodelling and histone m RNA accumulation in bovine germinal vesicle oocytes. Molecular reproduction and development 41 25940597
2014 Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM-Chk1/2-Cdc25C pathway. Toxicology and applied pharmacology 36 25450480
2021 Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways. Frontiers in pharmacology 35 33628174
2010 Activation of checkpoint kinase 2 by 3,3'-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells. Molecular pharmacology 35 20444961
2010 Gallic acid induces G2/M phase cell cycle arrest via regulating 14-3-3β release from Cdc25C and Chk2 activation in human bladder transitional carcinoma cells. Molecular nutrition & food research 35 20564478
2022 ALKBH1-mediated m1 A demethylation of METTL3 mRNA promotes the metastasis of colorectal cancer by downregulating SMAD7 expression. Molecular oncology 33 36550779
2017 Biochemical Characterization of AP Lyase and m6A Demethylase Activities of Human AlkB Homologue 1 (ALKBH1). Biochemistry 26 28290676
2022 High-dose zearalenone exposure disturbs G2/M transition during mouse oocyte maturation. Reproductive toxicology (Elmsford, N.Y.) 24 35504548
2019 Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells. Food & function 24 31617531
2021 Elevated TAB182 enhances the radioresistance of esophageal squamous cell carcinoma through G2-M checkpoint modulation. Cancer medicine 16 33787085
2013 Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell cycle progression. Cell cycle (Georgetown, Tex.) 14 24013421
2016 Oridonin promotes G2/M arrest in A549 cells by facilitating ATM activation. Molecular medicine reports 13 27959435
2016 Extracellular matrix metalloproteinase inducer (CD147/BSG/EMMPRIN)-induced radioresistance in cervical cancer by regulating the percentage of the cells in the G2/m phase of the cell cycle and the repair of DNA Double-strand Breaks (DSBs). American journal of translational research 12 27398135
1987 Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. VI. Detection of a non-MHC gene(s) in the E alpha-bearing RIIIS mouse strain that is associated with a specific lack of T cell responses to the M. arthritidis soluble mitogen. Journal of immunology (Baltimore, Md. : 1950) 10 3110289
2017 Pine needle oil induces G2/M arrest of HepG2 cells by activating the ATM pathway. Experimental and therapeutic medicine 7 29434792
2012 A novel MT-CO1 m.6498C>A variation associated with the m.7444G>A mutation in the mitochondrial COI/tRNA(Ser(UCN)) genes in a patient with hearing impairment, diabetes and congenital visual loss. Biochemical and biophysical research communications 6 23219819
2024 Fisetin induces G2/M phase arrest and caspase-mediated cleavage of p21Cip1 and p27Kip1 leading to apoptosis and tumor growth inhibition in HNSCC. Molecular carcinogenesis 4 38801393
2026 Acrylamide disrupts meiotic G2/M transition and SAC activity during oocyte maturation. Biology direct 1 41618314
2024 Indigofera suffruticosa aerial parts extract induce G2/M arrest and ATR/CHK1 pathway in Jurkat cells. BMC complementary medicine and therapies 1 38195460
2024 DNA Damage-Inducing 10-Methoxy-canthin-6-one (Mtx-C) Promotes Cell Cycle Arrest in G2/M and Myeloid Differentiation of Acute Myeloid Leukemias and Leukemic Stem Cells. ACS omega 1 39246489
2026 Comprehensive analysis of m6A-regulatory genes in soybean uncovers GmMTBa as a critical determinant of salinity stress tolerance. aBIOTECH 0 42022509
2026 Ac-SDKP Attenuates Silica-Induced Pulmonary Fibrosis by Inhibiting ALKBH1-Mediated m6A Demethylation of miR-129-5p. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 42172441
2025 Evodiamine induces centrosome amplification with subsequent G2/M cell cycle arrest in primary vascular smooth muscle cells. Biochemical pharmacology 0 40935161
2025 Association of genetic variants in m1A modification core genes and neuroblastoma risk. BMC cancer 0 41107791
2025 Demethylase, ALKBH1, regulates osteosarcoma chemosensitivity through FZD8/Wnt/β-catenin signaling pathway in the m7G manner. International journal of biological macromolecules 0 41274478
2023 Inhibition of HIST1H2AB suppresses the proliferation of lung adenocarcinoma. The journal of gene medicine 0 36511295

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